Procedural sedation is a standard technique used to manage acute pain and anxiety for spontaneously breathing adults and children undergoing medical procedures outside the operating room and intensive care unit. Procedural sedation differs from general anesthesia which suppresses central nervous system activity and results in unconsciousness and lack of sensation. Monitoring of anesthesia is described generally in PCT Patent Publication WO 2012/171610 by Kochs et al., U.S. Pat. No. 8,326,545 by Yudkovitch et al., U.S. Pat. No. 7,878,982 by Frank et al., U.S. Pat. No. 7,997,269 by Yudkovitch et al., US Patent Publication No. 2011/0118619 by Burton et al., WO 2011/017778 by Burton, U.S. Pat. No. 7,693,697 by Westenskow et al., US Patent Publication No. 2010/0169063 by Yudkovitch et al., and US Patent Publication No. 2008/0091084 by Yudkovitch et al., all of which are incorporated herein by reference.
In clinical settings where patients are sedated for medical procedures, i.e., undergoing procedural sedation, clinicians rely on qualitative methods to assess sedation state and track changes in the level of sedation of the patient, as well as any abnormal respiratory reaction. For example, clinicians may tap a patient on the shoulder or try to communicate with the patient in order to use degree of responsiveness as a surrogate measure for sedation level. These qualitative methods may be insufficient to detect patient oversedation, which can lead to respiratory compromise, or patient undersedation, which can result in unnecessary pain or anxiety. These qualitative approaches are limited and subjective as they are dependent on each clinician's acumen and experience in assessing sedation level, and therefore cannot be transferred from one clinical setting to another. Existing methods of monitoring in procedural sedation are not quantitative in nature, and, in particular, underutilize the capabilities of capnography and pharmacokinetic/pharmacodynamic modeling. The assessment of patient state during procedural sedation using electroencephalogram (EEG) signals is described in US Patent Publication No. 2007/0010756 by Viertio-Oja et al. However, EEG-derived sedation levels such as the bispectral index have not proven useful for assessing the lighter levels of sedation attained during procedural sedation, and are not used in current procedural sedation practice. Additionally, EEG is not generally monitored during procedural sedation. In the context of procedural sedation, US Patent App. Pub. No. 2010/0212666 by Bouillon et al. describes a controller apparatus and drug delivery system. The aforementioned applications are incorporated herein by reference as prior art that describe the use of pharmacokinetic models in the procedural sedation environment. However, both of these patent applications describe the use of pharmacokinetic model outputs to administer sedative agents in a closed-loop system. The system and methods proposed here instead claim the use of pharmacokinetic model outputs to guide drug titration with clinician input. Compartmental concentrations and/or corresponding sedation levels estimated by the pharmacokinetic or pharmacodynamic models will be presented to a clinician and serve as a recommendation or guidance system.
Capnography refers to the noninvasive measurement of the concentration of carbon dioxide, [CO2], in exhaled breath. Carbon dioxide is a byproduct of tissue metabolism. The [CO2] in exhaled breath can be measured noninvasively as a function of time or of volume. These measurement processes are respectively called time-based and volumetric capnography. Capnography monitors can be found in every properly equipped operating room, intensive care unit, and emergency department, as monitoring [CO2] in patients is an essential aspect of modern respiratory care, for example, to confirm successful endotracheal intubation. The waveform produced during capnography is called a capnogram and reflects underlying respiratory dynamics. However, currently only a small portion of the wealth of information contained in the capnogram is extracted and processed for use by clinicians.
Pharmacokinetic modeling describes the estimation of relevant physiological concentrations following drug administration. Pharmacodynamic modeling refers to the mapping of physiological drug concentrations to a predicted effect. Both pharmacokinetic and pharmacodynamic models have been used to estimate resulting physiological concentrations and effects following the administration of sedation agents, including propofol1 and ketamine2. However, the resulting effect outputs of pharmacodynamic models have typically been correlated with the bispectral index3, an EEG-derived quantity that is not found to be useful at the lighter levels of sedation experienced during procedural sedation4. Pharmacokinetic and pharmacodynamic models are particular to the type of drug administered, and model parameters vary due to patient-specific covariates such as age and weight. Such models typically contain multiple compartments that describe the differing drug metabolism and equilibration across various tissues and organ systems. 1 Schüttler, Jürgen, and Harald Ihmsen “Population Pharmacokinetics of Propofol: A Multicenter Study.” The Journal of the American Society of Anesthesiologists 92.3 (2000): 727-738.2 Herd, David W., et al. “Investigating the pharmacodynamics of ketamine in children.” Pediatric Anesthesia 18.1 (2008): 36-42.3 Lysakowski, Christopher, et al. “Bispectral and spectral entropy indices at propofol-induced loss of consciousness in young and elderly patients.” British journal of anaesthesia 103.3 (2009): 387-393.4 Gill, Michelle, Steven M. Green, and Baruch Krauss. “A study of the bispectral index monitor during procedural sedation and analgesia in the emergency department.” Annals of emergency medicine 41.2 (2003): 234-241.